Pathophysiology of motor symptoms, cognitive impairments, and psychosis in Parkinson's disease (PD) was reviewed. To understand pathophysiology of motor symptoms in PD, two major models have been proposed. In firing rate model, depletion of striatal dopamine decreases neural activity in the direct pathway from striatum to GPi/SNr and increases neural activity in the indirect pathway via GPe and STN, resulting in greater inhibition of motor thalamus that facilitate corticospinal motor output. This model has led to a new surgical treatment for PD, though there is emerging evidence that criticize the model. In a new model, called oscillation (firing pattern) model, loss of dopamine develops or enhances pathological oscillations in the beta band in STN and GPi, leading to suppression of movement. This model explains treatment effect of STN stimulation at 130Hz used in the deep brain stimulation since the stimulation should suppress the pathological beta band oscillation and improve motor symptom in PD. Cognitive impairments in PD affect various domains while deficits in visuospatial and executive function are frequent. PD psychosis represents a spectrum of illusions, passage/presence hallucinations, formed visual hallucinations and delusions that often progress over the course of PD.

The diagnosis of Parkinson's disease (PD) is based on clinical features. The UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (UKPDSBB criteria) were proposed in 1988, and have been commonly used around the world. Since publication of UKPDSBB criteria and other previous criteria, knowledge about PD has increased and several limitations have been found. In 2015, The International Parkinson and Movement Disorder Society (MDS) offered novel clinical diagnostic criteria for Parkinson's Disease (MDS–PD criteria). We summarize the main points of the MDS–PD criteria, including the utility and limitations of those.

Parkinson's disease is a neurodegenerative disease cardinally showing movement disorders. Motor symptoms are manifested by magnification of Lewy pathology into the substantia nigra pars compacta, which induces dopaminergic neuronal loss and dopamine deficiency in the nigro–striatal dopaminergic projection. Therefore, dopamine replacement therapy is the gold standard in pharmacotherapy in Parkinson's disease. Now a days, dopaminergic agonists, dopamine economizers as well as non–dopaminergic agents are clinically available in Japan. Drug delivery systems have also been improving. Transdermal and intrajejunal formulations are available in Japan, whereas subcutaneous continuous injection, inhaler and sublingual film are available and developing in foreign countries. Most of them are based on the therapeutical concept of continuous dopaminergic stimulation. Neuromodulation and exercise are also important therapeutic interventions in motor treatment in Parkinson's disease. Deep brain stimulation and L–dopa carbidopa intestinal gel are categorized as device–aided therapy, which are applicable to advanced stage. Next to the advanced stage, late stage will inevitably come and variable refractory problems in this stage can deteriorate qualities of life. The qualities of life in the late stage can come at the expense of pharmacotherapy of motor symptoms, which should be established on the well–organized communication and an advanced adherence among patients, physicians, and care givers.

Nonmotor symptoms (NMS) have increasingly been recognized as an important part of Parkinson disease (PD). Although NMS are very common across all stages of PD, NMS are frequently undeclared from the patients, often under–recognized by the clinicians and remain untreated. The burden of NMS can define a patient's health–related quality of life. The management of NMS has been recognized as an important area of unmet needs in PD. There is a broad spectrum of NMS in PD, which include neuro–psychiatric disturbance (hallucination, delirium, delusion, impulse control disorders, cognitive dysfunction, dementia), autonomic dysfunction (orthostatic hypotension, constipation, urinary dysfunction, sexual dysfunction, hyperhydrosis), sleep disturbance (insomnia, excessive daytime sleepiness, sudden onset of sleep, REM sleep behavior disorders, restless legs syndrome), mood disorders (depression, anxiety, apathy), fatigue and sensory disturbance (pain, smell loss). Although the importance of a dopaminergic contribution to NMS in PD has been highlighted, the NMS of PD include a multitude of clinical systems derived from complex multi–neurotransmitter dysfunction involving not just the dopaminergic pathways but also noradrenergic, serotonergic and cholinergic pathways in the brain. In addition to the evolution of NMS as an intrinsic part of the disease, treatment used in PD can trigger, worsen, or even be the primary cause of symptoms. The symptoms and treatments of NMS in PD are often multiple and complex. The Japanese “PD clinical guideline 2018” updates the previous PD treatment guideline 2011 and incorporates new data on efficacy, safety, and implications for clinical practice of treatments for NMS of PD. By using the current evidence in the medical literature, evidence–based medicine helps to provide the best possible care to patients. Although there has been a number of placebo–controlled randomized trials of treatments of PD–related NMS and the evidence base for treating a range of NMS in PD has grown substantially in recent years, many nonmotor areas still lack an adequate evidence base of high–quality studies.

The aim of the article is to describe the revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) in 2017. The criteria for the clinical diagnosis of DLB were first published as the first consensus report in 1996, and were revised in the third consensus report in 2005. After discussion in the International DLB Conference in 2015, the International DLB Consortium published the fourth consensus report including the revised consensus criteria in 2017. The 2017 revised criteria distinguish clearly between clinical features and diagnostic biomarkers and give guidance about optimal methods to establish and interpret these. Diagnostic weighting of REM sleep behaviour disorder (RBD) and iodine–123–metaiodobenzylguanidine (MIBG) myocardial scintigraphy was increased. Future directions include development of the criteria for early diagnosis (prodromal and preclinical DLB) and pathological evaluation of diagnostic accuracy of the 2017 revised diagnostic criteria.

Dementia with Lewy bodies (DLB) causes various symptoms such as psychiatric symptoms, parkinsonism, and failures of autonomic nervous system in addition to cognitive impairment, all of which are clinical and care problems. This review provides evidence–based commentary on treatment of DLB. Donepezil has been the central means since its approval in 2014 for the treatment of cognitive impairment of DLB, and evidence of it is accumulating and gives clues of the usage of it. Although there is insufficient evidence on the efficacy of donepezil for BPSD, it is still the first choice before antipsychotics. On the other hand, motor disorders due to parkinsonism are also important therapeutic targets. Levodopa is the mainstay of treatment. Recently, multicenter, placebo–controlled, randomizeouble–blind, controlled trials have shown the efficacy of adding zonisamide over levodopa treatment for parkinsonism in DLB. Unfortunately, there is no high level of evidence of treatment for a variety of other conditions, and individual patients will be treated with knowledge of other diseases.

A–37–year–old man with a history of migraine without aura developed his ear fullness (day 1). On day 3, he developed dizziness, headache which worsened when he stood up, and vomiting. Rizatriptan was ineffective. Brain magnetic resonance imaging showed no abnormality and he visited otorhinolaryngology. He had no nystagmus. An audiogram revealed his left low–tone hearing loss. Ménière's disease was suspected, and isosorbide was started. Headache with dizziness diminished gradually. On day 13, the audiogram showed no abnormality, and other symptoms disappeared on day 20. Hearing loss without headache recurred after 7 months. The symptom was relieved by adenosine triphosphate disodium hydrate. Afterward, he had no relapse. Differential diagnosis initially included vestibular migraine. Eventually, the headache persisted for more than 72 hours, and a vestibular migraine was excluded. Headache was considered to be due to Ménière's disease. Migraine is often associated with Ménière's disease. If a patient with migraine shows a headache with dizziness, not only a vestibular migraine but also Ménière's disease should be considered.

We performed unilateral MRI–guided focused ultrasound (MRgFUS) thalamotomy for 10 medication–refractory essential tremor patients (8 men and 2 women, aged 67.1 ± 17.5 years, right–handed), and evaluated the efficacy and adverse events during a 12–month follow–up. Right–handed tremor improved immediately after left ventral intermediate nucleus (Vim) thalamotomy in all patients. Tremor re–exacerbated in 2 patients after 3 and 6 months, respectively ; however, the average score of the clinical rating scale for tremor maintained an about 60% decline from the baseline at 12 months. On the other hand, the average global impression score of the quality of life in essential tremor questionnaire showed no improvement. Most of the adverse events were mild and transient, however, sensory impairment in 2 patients persisted up to 3 months later. There were no delayed complications related to MRgFUS thalamotomy from 6 to 12 months after the procedure. Unilateral MRgFUS Vim thalamotomy could be adopted as one of the therapeutic options for intractable essential tremor.

We studied the effect of the physical therapy using a balance adjustment system (BASYS) for gait disturbance in patients with Parkinson disease (PD) and spinocerebellar degeneration (SCD). Four PD patients and 4 SCD patients were analyzed. We measured the number of steps, time (second) and 10m walking speed (m/s) before and after physical therapy using BASYS. We carried out the second study 5 to 7 days after the first study. In the first study, the number of steps, time and speed before/after physiotherapy were 26.50 ± 8.20/24.13 ± 6.72 (mean ± SD), 14.55 ± 5.08/12.59 ± 3.84 and 0.77 ± 0.25/0.87 ± 0.27, respectively. In the second study, the results were 23.62 ± 6.26/21.50 ± 5.61, 12.12 ± 3.19/10.56 ± 2.79 and 0.89 ± 0.24/1.02 ± 0.28, respectively. A Wilcoxon signed–rank test revealed significant differences at each time point ; however, no significant difference was found between the results obtained after the first study and before the second study. These findings revealed that the physical therapy with the BASYS improved gait disturbance in patients with PD and SCD, and that the efficacy continued for 5 to 7 days. Afferents from spindles and stretch reflex in the extensor and flexor muscles of the lower legs might modify the spinal neural system, generating the locomotive motor output. Further investigations are needed to prove the effect of the BASYS on gait disturbance in patients with neurodegenerative disease and to clarify the mechanism of its effect.